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Adipose Tissue and Adipokines in Health and Disease pp 115–127Cite as

Autophagy in White Adipose Tissue

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Part of the book series: Nutrition and Health ((NH))

Abstract

Autophagy is a mechanism for intracellular degradation of cytoplasmic components including macromolecules and organelles. It has been shown to be involved in a large number of physiological and pathological processes. Studies have recently uncovered an important role of autophagy in the process of adipogenesis. In addition, some interesting correlations between autophagy activity and adipose functions have been made. This chapter explores the roles autophagy plays in adipocytes, detailing the core machinery of autophagy and highlighting what is currently understood about the functions of autophagy in differentiating and mature white adipocytes.

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References

  1. Nakagawa I, et al. Autophagy defends cells against invading group A Streptococcus. Science. 2004;306:1037.

    Article  PubMed  CAS  Google Scholar 

  2. Paludan C, et al. Endogenous MHC class II processing of a viral nuclear antigen after autophagy. Science. 2005;307:593.

    Article  PubMed  CAS  Google Scholar 

  3. Klionsky DJ. Autophagy: from phenomenology to molecular understanding in less than a decade. Nat Rev Mol Cell Biol. 2007;8:931.

    Article  PubMed  CAS  Google Scholar 

  4. Yue ZY, Jin SK, Yang CW, Levine AJ, Heintz N. Beclin 1, an autophagy gene essential for early embryonic development, is a haploinsufficient tumor suppressor. Proc Natl Acad Sci U S A. 2003;100:15077.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  5. Tsujimoto Y, Shimizu S. Another way to die: autophagic programmed cell death. Cell Death Differ. 2005;12:1528.

    Article  PubMed  CAS  Google Scholar 

  6. Penka M, et al. [Essential thrombocytemia and other myeloproliferations with thrombocytemia in the data of the register of patients treated with Thromboreductin till the end of 2006]. Vnitr Lek. 2007;53:653.

    PubMed  CAS  Google Scholar 

  7. Kissova I, et al. Selective and non-selective autophagic degradation of mitochondria in yeast. Autophagy. 2007;3:329.

    PubMed  CAS  Google Scholar 

  8. Cuervo AM, et al. Autophagy and aging: the importance of maintaining “clean” cells. Autophagy. 2005;1:131.

    Article  PubMed  Google Scholar 

  9. Kroemer G, Marino G, Levine B. Autophagy and the integrated stress response. Mol Cell. 2010;40:280.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  10. Rubinszfein DC, et al. Autophagy and its possible roles in nervous system diseases, damage and repair. Autophagy. 2005;1:11.

    Article  Google Scholar 

  11. Mizushima N, Levine B. Autophagy in mammalian development and differentiation. Nat Cell Biol. 2010;12:823.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  12. Tsukada M, Ohsumi Y. Isolation and characterization of autophagy-defective mutants of Saccharomyces cerevisiae. FEBS Lett. 1993;333:169.

    Article  PubMed  CAS  Google Scholar 

  13. Yang Z, Klionsky DJ. Eaten alive: a history of macroautophagy. Nat Cell Biol. 2010;12:814.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  14. Mizushima N, Yoshimori T, Ohsumi Y. The role of Atg proteins in autophagosome formation. Annu Rev Cell Dev Biol. 2011;27:107.

    Article  PubMed  CAS  Google Scholar 

  15. Kamada Y, et al. Tor directly controls the Atg1 kinase complex to regulate autophagy. Mol Cell Biol. 2010;30:1049.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  16. Pattingre S, Espert L, Biard-Piechaczyk M, Codogno P. Regulation of macroautophagy by mTOR and Beclin 1 complexes. Biochimie. 2008;90:313.

    Article  PubMed  CAS  Google Scholar 

  17. Efeyan A, Sabatini DM. mTOR and cancer: many loops in one pathway. Curr Opin Cell Biol. 2010;22:169.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  18. Yang Z, Klionsky DJ. Mammalian autophagy: core molecular machinery and signaling regulation. Curr Opin Cell Biol. 2010;22:124.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  19. He C, Levine B. The Beclin 1 interactome. Curr Opin Cell Biol. 2010;22:140.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  20. Axe EL, et al. Autophagosome formation from membrane compartments enriched in phosphatidylinositol 3-phosphate and dynamically connected to the endoplasmic reticulum. J Cell Biol. 2008;182:685.

    Article  PubMed Central  PubMed  Google Scholar 

  21. Polson HE, et al. Mammalian Atg18 (WIPI2) localizes to omegasome-anchored phagophores and positively regulates LC3 lipidation. Autophagy. 2010;6:506.

    Article  PubMed  CAS  Google Scholar 

  22. Tooze SA, Yoshimori T. The origin of the autophagosomal membrane. Nat Cell Biol. 2010;12:831.

    Article  PubMed  CAS  Google Scholar 

  23. Xie Z, Nair U, Klionsky DJ. Dissecting autophagosome formation: the missing pieces. Autophagy. 2008;4:920.

    PubMed  CAS  Google Scholar 

  24. Yang Z, Klionsky DJ. An overview of the molecular mechanism of autophagy. Curr Top Microbiol Immunol. 2009;335:1.

    PubMed Central  PubMed  CAS  Google Scholar 

  25. Klionsky DJ, et al. Guidelines for the use and interpretation of assays for monitoring autophagy in higher eukaryotes. Autophagy. 2008;4:151.

    PubMed Central  PubMed  CAS  Google Scholar 

  26. Huang WP, Scott SV, Kim J, Klionsky DJ. The itinerary of a vesicle component, Aut7p/Cvt5p, terminates in the yeast vacuole via the autophagy/Cvt pathways. J Biol Chem. 2000;275:5845.

    Article  PubMed  CAS  Google Scholar 

  27. Noda T, et al. Apg9p/Cvt7p is an integral membrane protein required for transport vesicle formation in the Cvt and autophagy pathways. J Cell Biol. 2000;148:465.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  28. Mortimore GE, Schworer CM. Induction of autophagy by amino-acid deprivation in perfused rat liver. Nature. 1977;270:174.

    Article  PubMed  CAS  Google Scholar 

  29. Schworer CM, Mortimore GE. Glucagon-induced autophagy and proteolysis in rat liver: mediation by selective deprivation of intracellular amino acids. Proc Natl Acad Sci U S A. 1979;76:3169.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  30. Surmacz CA, Poso AR, Mortimore GE. Regulation of lysosomal fusion during deprivation-induced autophagy in perfused rat liver. Biochem J. 1987;242:453.

    PubMed Central  PubMed  CAS  Google Scholar 

  31. Levine B, Kroemer G. Autophagy in the pathogenesis of disease. Cell. 2008;132:27.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  32. Mizushima N, Levine B, Cuervo AM, Klionsky DJ. Autophagy fights disease through cellular self-digestion. Nature. 2008;451:1069.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  33. Lum JJ, DeBerardinis RJ, Thompson CB. Autophagy in metazoans: cell survival in the land of plenty. Nat Rev Mol Cell Biol. 2005;6:439.

    Article  PubMed  CAS  Google Scholar 

  34. Kalamidas SA, Kotoulas OB. Glycogen autophagy in newborn rat hepatocytes. Histol Histopathol. 2000;15:1011.

    PubMed  CAS  Google Scholar 

  35. Clark Jr SL. Cellular differentiation in the kidneys of newborn mice studies with the electron microscope. J Biophys Biochem Cytol. 1957;3:349.

    Article  PubMed Central  PubMed  Google Scholar 

  36. Novikoff AB. The proximal tubule cell in experimental hydronephrosis. J Biophys Biochem Cytol. 1959;6:136.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  37. Ashford TP, Porter KR. Cytoplasmic components in hepatic cell lysosomes. J Cell Biol. 1962;12:198.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  38. Lemasters JJ. Perspective—selective mitochondrial autophagy, or mitophagy, as a targeted defense against oxidative stress, mitochondrial dysfunction, and aging. Rejuvenation Res. 2005;8:3.

    Article  PubMed  CAS  Google Scholar 

  39. Narendra DP, et al. PINK1 is selectively stabilized on impaired mitochondria to activate Parkin. PLoS Biol. 2010;8:e1000298.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  40. Jin SM, et al. Mitochondrial membrane potential regulates PINK1 import and proteolytic destabilization by PARL. J Cell Biol. 2010;191:933.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  41. Narendra D, Tanaka A, Suen DF, Youle RJ. Parkin is recruited selectively to impaired mitochondria and promotes their autophagy. J Cell Biol. 2008;183:795.

    Article  PubMed Central  PubMed  Google Scholar 

  42. Chan NC, et al. Broad activation of the ubiquitin-proteasome system by Parkin is critical for mitophagy. Hum Mol Genet. 2011;20:1726.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  43. Geisler S, et al. PINK1/Parkin-mediated mitophagy is dependent on VDAC1 and p62/SQSTM1. Nat Cell Biol. 2010;12:119.

    Article  PubMed  CAS  Google Scholar 

  44. Narendra D, Kane LA, Hauser DN, Fearnley IM, Youle RJ. p62/SQSTM1 is required for Parkin-induced mitochondrial clustering but not mitophagy; VDAC1 is dispensable for both. Autophagy. 2010;6:1090.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  45. Tanaka A, et al. Proteasome and p97 mediate mitophagy and degradation of mitofusins induced by Parkin. J Cell Biol. 2010;191:1367.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  46. Ding WX, et al. Linking of autophagy to ubiquitin-proteasome system is important for the regulation of endoplasmic reticulum stress and cell viability. Am J Pathol. 2007;171:513.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  47. Verfaillie T, Salazar M, Velasco G, Agostinis P. Linking ER stress to autophagy: potential implications for cancer therapy. Int J Cell Biol. 2010;2010:930509.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  48. Qin L, Wang Z, Tao L, Wang Y. ER stress negatively regulates AKT/TSC/mTOR pathway to enhance autophagy. Autophagy. 2010;6:239.

    Article  PubMed  CAS  Google Scholar 

  49. Sakaki K, Wu J, Kaufman RJ. Protein kinase Ctheta is required for autophagy in response to stress in the endoplasmic reticulum. J Biol Chem. 2008;283:15370.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  50. Ogata M, et al. Autophagy is activated for cell survival after endoplasmic reticulum stress. Mol Cell Biol. 2006;26:9220.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  51. Hotamisligil GS. Endoplasmic reticulum stress and the inflammatory basis of metabolic disease. Cell. 2010;140:900.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  52. Leem J, Koh EH. Interaction between mitochondria and the endoplasmic reticulum: implications for the pathogenesis of type 2 diabetes mellitus. Exp Diabetes Res. 2012;2012:242984.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  53. Scherz-Shouval R, Elazar Z. Regulation of autophagy by ROS: physiology and pathology. Trends Biochem Sci. 2011;36:30.

    Article  PubMed  CAS  Google Scholar 

  54. Huang J, Lam GY, Brumell JH. Autophagy signaling through reactive oxygen species. Antioxid Redox Signal. 2011;14:2215.

    Article  PubMed  CAS  Google Scholar 

  55. Scherz-Shouval R, et al. Reactive oxygen species are essential for autophagy and specifically regulate the activity of Atg4. EMBO J. 2007;26:1749.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  56. Zhang H, et al. Oxidative stress induces parallel autophagy and mitochondria dysfunction in human glioma U251 cells. Toxicol Sci. 2009;110:376.

    Article  PubMed  CAS  Google Scholar 

  57. Byun YJ, et al. Hydrogen peroxide induces autophagic cell death in C6 glioma cells via BNIP3-mediated suppression of the mTOR pathway. Neurosci Lett. 2009;461:131.

    Article  PubMed  CAS  Google Scholar 

  58. Jain A, et al. p62/SQSTM1 is a target gene for transcription factor NRF2 and creates a positive feedback loop by inducing antioxidant response element-driven gene transcription. J Biol Chem. 2010;285:22576.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  59. Komatsu M, et al. The selective autophagy substrate p62 activates the stress responsive transcription factor Nrf2 through inactivation of Keap1. Nat Cell Biol. 2010;12:213.

    PubMed  CAS  Google Scholar 

  60. Lau A, et al. A noncanonical mechanism of Nrf2 activation by autophagy deficiency: direct interaction between Keap1 and p62. Mol Cell Biol. 2010;30:3275.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  61. Cherra III SJ, Chu CT. Autophagy in neuroprotection and neurodegeneration: a question of balance. Future Neurol. 2008;3:309.

    PubMed Central  PubMed  Google Scholar 

  62. Bove J, Martinez-Vicente M, Vila M. Fighting neurodegeneration with rapamycin: mechanistic insights. Nat Rev Neurosci. 2011;12:437.

    Article  PubMed  CAS  Google Scholar 

  63. Chen HY, White E. Role of autophagy in cancer prevention. Cancer Prev Res (Phila). 2011;4:973.

    Article  CAS  Google Scholar 

  64. Orvedahl A, Levine B. Eating the enemy within: autophagy in infectious diseases. Cell Death Differ. 2009;16:57.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  65. Heynen MJ, Tricot G, Verwilghen RL. Autophagy of mitochondria in rat bone marrow erythroid cells. Relation to nuclear extrusion. Cell Tissue Res. 1985;239:235.

    Article  PubMed  CAS  Google Scholar 

  66. Chen M, Sandoval H, Wang J. Selective mitochondrial autophagy during erythroid maturation. Autophagy. 2008;4:926.

    PubMed Central  PubMed  CAS  Google Scholar 

  67. Sandoval H, et al. Essential role for Nix in autophagic maturation of erythroid cells. Nature. 2008;454:232.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  68. Schweers RL, et al. NIX is required for programmed mitochondrial clearance during reticulocyte maturation. Proc Natl Acad Sci U S A. 2007;104:19500.

    Article  PubMed Central  PubMed  Google Scholar 

  69. Zhang J, Ney PA. NIX induces mitochondrial autophagy in reticulocytes. Autophagy. 2008;4:354.

    PubMed  Google Scholar 

  70. Pua HH, Guo J, Komatsu M, He YW. Autophagy is essential for mitochondrial clearance in mature T lymphocytes. J Immunol. 2009;182:4046.

    Article  PubMed  Google Scholar 

  71. Bassnett S. On the mechanism of organelle degradation in the vertebrate lens. Exp Eye Res. 2009;88:133.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  72. Friedman JM. Leptin at 14 y of age: an ongoing story. Am J Clin Nutr. 2009;89:973s.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  73. Rosen ED, Spiegelman BM. Adipocytes as regulators of energy balance and glucose homeostasis. Nature. 2006;444:847.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  74. Kadowaki T, Yamauchi T. Adiponectin and adiponectin receptors. Endocr Rev. 2005;26:439.

    Article  PubMed  CAS  Google Scholar 

  75. Kahn SE, Hull RL, Utzschneider KM. Mechanisms linking obesity to insulin resistance and type 2 diabetes. Nature. 2006;444:840.

    Article  PubMed  CAS  Google Scholar 

  76. Park KW, Halperin DS, Tontonoz P. Before they were fat: adipocyte progenitors. Cell Metab. 2008;8:454.

    Article  PubMed  CAS  Google Scholar 

  77. Rosen ED, Spiegelman BM. Molecular regulation of adipogenesis. Annu Rev Cell Dev Biol. 2000;16:145.

    Article  PubMed  CAS  Google Scholar 

  78. Agarwal AK, Garg A. A novel heterozygous mutation in peroxisome proliferator-activated receptor-gamma gene in a patient with familial partial lipodystrophy. J Clin Endocrinol Metab. 2002;87:408.

    PubMed  CAS  Google Scholar 

  79. Imai T, et al. Peroxisome proliferator-activated receptor gamma is required in mature white and brown adipocytes for their survival in the mouse. Proc Natl Acad Sci U S A. 2004;101:4543.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  80. Novikoff AB, Novikoff PM, Rosen OM, Rubin CS. Organelle relationships in cultured 3T3-L1 preadipocytes. J Cell Biol. 1980;87:180.

    Article  PubMed  CAS  Google Scholar 

  81. Zhang Y, et al. Adipose-specific deletion of autophagy-related gene 7 (atg7) in mice reveals a role in adipogenesis. Proc Natl Acad Sci U S A. 2009;106:19860.

    Article  PubMed Central  PubMed  Google Scholar 

  82. Singh R, et al. Autophagy regulates adipose mass and differentiation in mice. J Clin Invest. 2009;119:3329.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  83. Baerga R, Zhang Y, Chen PH, Goldman S, Jin S. Targeted deletion of autophagy-related 5 (atg5) impairs adipogenesis in a cellular model and in mice. Autophagy. 2009;5:1118.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  84. Wilson-Fritch L, et al. Mitochondrial biogenesis and remodeling during adipogenesis and in response to the insulin sensitizer rosiglitazone. Mol Cell Biol. 2003;23:1085.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  85. Yoshizaki T, et al. Autophagy regulates inflammation in adipocytes. Biochem Biophys Res Commun. 2012;417:352.

    Article  PubMed  CAS  Google Scholar 

  86. Solomon VR, Lee H. Chloroquine and its analogs: a new promise of an old drug for effective and safe cancer therapies. Eur J Pharmacol. 2009;625:220.

    Article  PubMed  CAS  Google Scholar 

  87. Wasko MC, et al. Hydroxychloroquine and risk of diabetes in patients with rheumatoid arthritis. JAMA. 2007;298:187.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Veterinary Pathology, Mount Ida College, U.S. Army Research Institute of Environmental Medicine, Natick, MA, 01760, USA

    Scott G. Goldman

  2. Robert Wood Johnson Medical School, Rutgers University, 675 Hoes Lane, R506, Piscataway, NJ, 08854, USA

    Hanlin Tao

  3. Department of Pharmacology, Robert Wood Johnson Medical School, Rutgers University, 675, Hoes Lane West, Research Tower, R501/503, Piscataway, NJ, 08854, USA

    Shengkan ‘Victor’ Jin Ph.D.

Authors
  1. Scott G. Goldman
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  2. Hanlin Tao
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  3. Shengkan ‘Victor’ Jin Ph.D.
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Corresponding authors

Correspondence to Scott G. Goldman or Shengkan ‘Victor’ Jin Ph.D. .

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Editors and Affiliations

  1. Department of Kinesiology and Nutrition, University of Illinois at Chicago, Chicago, Illinois, USA

    Giamila Fantuzzi

  2. Department of Kinesiology and Nutrition, University of Illinois at Chicago, Chicago, Illinois, USA

    Carol Braunschweig

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Goldman, S.G., Tao, H., Jin, S.‘. (2014). Autophagy in White Adipose Tissue. In: Fantuzzi, G., Braunschweig, C. (eds) Adipose Tissue and Adipokines in Health and Disease. Nutrition and Health. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-770-9_9

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  • DOI: https://doi.org/10.1007/978-1-62703-770-9_9

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